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*It is only for medical professionals to read for reference and is worth collecting! In the treatment of acute ischemic stroke (AIS), thrombolysis and thrombectomy have become the main treatment methods, and anticoagulation therapy seems to gradually fade out of people's sight
.
What is the role of anticoagulant therapy in the early treatment of AIS? At the 24th National Neurology Academic Conference of the Chinese Medical Association, Professor Zhang Meng from Daping Hospital of the Army Military Medical University sorted out the relevant content of AIS early anticoagulation in detail, including anticoagulation before, during and after thrombus removal.
He also shared his own clinical practice experience
.
Anticoagulation before thrombus removal.
Review the development process of anticoagulation drugs (Figure 1).
From the earliest unfractioned heparin (UFH) to the direct factor Xa antagonist for more than ten years, anticoagulation drugs have moved from multiple targets to Single-target therapy transitions while ensuring its activity and safety
.
Figure 1: The development process of anticoagulant drugs (picture from Professor Zhang Meng's PPT) ■ The previous research PROACT study, namely Prolyse in Acute Cerebral Thromboembolism, is a milestone study of arterial thrombolysis.
Both studies used the anticoagulant drug UFH
.
The results of the PROACT Ⅰ study showed that 81.
8% of patients in the high-dose UFH (100 IU/kg bolus+1000 IU/h×4 h) group achieved vascular recanalization (TIM1 blood flow classification 2 and 3), and the incidence of intracranial hemorrhage was 27.
3 %; In the low-dose group (2000 IU Bolus+500 IU/h×4 h), the incidence of intracranial hemorrhage dropped to 6.
7%, but the recanalization rate also dropped to 40% [1]
.
The results of the PROACTⅡ study showed that intraarterial administration of recombinant prourokinase (rPro-UK) combined with UFH within 6 hours of acute cerebral infarction compared with low-dose UFH, although increased the incidence of intracranial hemorrhage, can significantly improve the 90-day good prognosis [ 2]
.
In 2015, a systematic review reviewed 24 RCT studies on early anticoagulation treatment of AlS from 2008 to 2014, (21 of which used UFH), 23748 patients, and the results showed that anticoagulation therapy can reduce the recurrence rate of AlS , Pulmonary embolism and deep vein thrombosis rates, but are offset by the increased risk of intracranial hemorrhage [3]
.
Current guidelines, such as the 2019 AHA/ASA Guidelines for Early Management of Acute Ischemic Stroke, do not recommend emergency anticoagulation for patients with acute ischemic stroke to prevent early stroke recurrence, deterioration of tissue and nerve function, or improve prognosis
.
■ Anticoagulation promotes the recovery of AIS patients-case sharing Although the guidelines do not recommend preoperative anticoagulation, in actual clinical practice, preoperative anticoagulation may be used to promote the recovery of patients
.
Professor Zhang shared similar cases .
The 52-year-old patient was admitted to the hospital for "dizziness, blurred vision for 5 days, and weakness of the right limb for 4 days"
.
The National Institutes of Health Stroke Scale (NIHSS) score was 13 points, and the ASPECT score was 3 points
.
The imaging examination is shown in Figure 2, and the internal carotid artery dissection is suspected
.
During the treatment, patients were given 3000u heparin before surgery, 0.
4ml Bid of low molecular weight heparin (LMWH) after surgery, and then transitioned to warfarin
.
The patient's treatment check result is shown in Figure 3
.
After 11 months of treatment, the patient's internal carotid artery repair effect was better (Figure 4)
.
This case shows that anticoagulation therapy has a significant effect on specific acute large vessel occlusion (LVO) AIS
.
Figure 2: Admission imaging examination (picture from Professor Zhang Meng's PPT) Figure 3: Patient treatment examination results (picture from Professor Zhang Meng's PPT) Figure 4: Comparison after 11 months of treatment (picture from Professor Zhang Meng's PPT) Embolectomy In 2018, Winningham et al.
retrospectively analyzed the TREVO2 trial.
53 patients (53/173) received an average of 3000 U intravenous UFH during the perioperative period.
The results showed that the 90-day good prognosis of patients was related to intravenous UFH, and intracranial hemorrhage occurred.
The rate difference is not statistically significant [4]
.
In the MR CLEAN study (ie, Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke Study), 1488 patients were analyzed in the same case.
Among them, 398 patients (27%) received intravenous UFH treatment (median dose 5000 U), two There was no significant difference in functional prognosis (Figure 5), successful recanalization rate, incidence of intracranial hemorrhage, and mortality between the groups.
However, the prognosis of patients is better in treatment centers with a higher proportion of UFH [5]
.
In these studies, the incidence of intracranial hemorrhage was between 5%-12%
.
Overall, the risk of intracranial hemorrhage seems to be offset by a higher overall good functional prognosis, suggesting that UFH may be beneficial to administering UFH during arterial therapy
.
Figure 5: Comparison of mRs scores between the two groups with and without heparin in the MR CLEAN study [5] Professor Zhang introduced the intraoperative heparin administration program in his center: For patients who did not receive intravenous thrombolysis before surgery, surgery started After that, UFH 3000U is usually given as an intravenous bolus, and 500U is added every hour thereafter
.
For patients who receive intravenous thrombolysis within 2 hours before surgery, UFH is generally not given.
For patients with an interval of more than 2 hours, depending on whether there is a tendency for hypercoagulability during surgery, an appropriate amount of UFH should be given
.
It is more reasonable to monitor the activated coagulation time (ACT) during the operation and adjust the dosage based on this
.
Anticoagulation after thrombus removal Although this part of the report is an anticoagulation strategy after thrombus removal, Professor Zhang mainly introduces anticoagulation treatment after stroke in patients with atrial fibrillation
.
■ The VISTA study on the timing of anticoagulation after the occurrence of AIS in atrial fibrillation (the Virtual International Stroke Trials Archive study) showed that vitamin K antagonist treatment started 2-3 days after the onset of stroke in patients with atrial fibrillation, compared with the start of use> 3 days, ischemic The probability of stroke recurrence is lower, and the 90-day functional recovery of the anticoagulation group is better [6]
.
The RAF-NOAC study (ie Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin-K Oral Anticoagulants study) shows that: most intracranial hemorrhage occurs in patients who initiate anticoagulation <3 days after stroke : The probability of stroke recurrence or bleeding in patients who started new oral anticoagulants within 2 days was 12.
4%, 2.
1% after 3-14 days, and 9.
1% after 14 days
.
However, these bleeding occurred 30 days after medication, and the relationship with early anticoagulation is not clear
.
In 2020, a systematic review analyzed the relevant literature on early anti-doubt treatment after stroke since 1990.
The systematic review pointed out [8]: The use of parenteral anticoagulants within 48 hours leads to an increased risk of hemorrhagic transformation and is not recommended; within 48 hours The use of new oral anticoagulants is associated with 5% of hemorrhage conversion.
There is not enough data to support the safety of starting conventional oral anticoagulants (new oral anticoagulants or warfarin) within 48 hours after AIS
.
■ Guidelines for the recommendation of anticoagulation after AIS in patients with atrial fibrillation.
The 2019 American Heart Association/American Stroke Association (AHA/ASA) early management guidelines for acute ischemic stroke are recommended for most patients with acute ischemic stroke with atrial fibrillation It is reasonable to start oral anticoagulation therapy between 4 and 14 days after the onset of neurological symptoms
.
The Chinese Guidelines for Endovascular Treatment of Acute Ischemic Stroke in China 2018 recommend that anticoagulation treatment after intravenous thrombolysis and intravascular treatment is still inconclusive.
Early anticoagulation treatment without choice is not recommended.
A few special patients are in You can choose carefully after carefully evaluating the risk-benefit ratio
.
For acute ischemic stroke caused by atrial fibrillation, it is reasonable to start anticoagulant therapy 4-14 days after the onset
.
In 2016, the European Heart Association recommended the 1-3-6-12 rule for the timing of starting or continuing anticoagulation therapy after a stroke or transient ischemic attack.
In simple terms, it means that the timing of the restart of a transient ischemic attack is after the occurrence1 Day, mild stroke (NIHSS <8 points) 3 days, moderate stroke (NIHSS score 8-15 points) 6 days, severe stroke (NIHSS ≥ 16 points) 12 days
.
See Figure 6 for details
.
Figure 6: Timing of starting or continuing anticoagulation after stroke or transient cerebral ischemia (picture adapted from Professor Zhang Meng's PPT) Professor Zhang concluded that the purpose of early anticoagulation after thrombus removal is to prevent reocclusion and improve microcirculation , That is, to block the vicious circle of blocked venous return and intracranial hypertension
.
Early anticoagulation treatment of AIS, to clarify the type of anticoagulation patient, the timing of anticoagulation, the type and dosage of anticoagulation drugs, we still need to continue to explore
.
The content of this article is compiled from the lecture of Professor Zhang Meng at the 24th National Neurology Conference of the Chinese Medical Association-"Thinking of Early Anticoagulation after AIS"
.
References: [1]del Zoppo GJ,Higashida RT,Furlan AJ,Pessin MS,Rowley HA,Gent M.
PROACT:a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke.
PROACT Investigators .
Prolyse in Acute Cerebral Thromboembolism.
Stroke.
1998;29(1):4-11.
[2]Furlan A,Higashida R,Wechsler L,et al.
Intra-arterial prourokinase for acute ischemic stroke.
The PROACT II study:a randomized controlled trial.
Prolyse in Acute Cerebral Thromboembolism.
JAMA.
1999;282(21):2003-2011.
[3]Sandercock PA,Counsell C,Kane EJ.
Anticoagulants for acute ischaemic stroke.
Cochrane Database Syst Rev.
2015;2015( 3):CD000024.
Published 2015 Mar 12.
[4]Winningham MJ,Haussen DC,Nogueira RG,et al.
Periprocedural heparin use in acute ischemic stroke endovascular therapy:the TREVO 2 trial.
J Neurointerv Surg.
2018;10(7) :611-614.
[5]van de Graaf RA,Chalos V,van Es ACGM,et al.
Periprocedural Intravenous Heparin During Endovascular Treatment for Ischemic Stroke: Results From the MR CLEAN Registry.
Stroke.
2019;50(8):2147-2155.
[6]Abdul-Rahim AH,Fulton RL,Frank B ,et al.
Association of improved outcome in acute ischaemic stroke patients with atrial fibrillation who receive early antithrombotic therapy:analysis from VISTA.
Eur J Neurol.
2015;22(7):1048-1055.
[7]Paciaroni M,Agnelli G, Falocci N, et al.
Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin-K Oral Anticoagulants(RAF-NOACs) Study.
J Am Heart Assoc.
2017;6(12):e007034.
[8]Smythe MA,Parker D,Garwood CL,Cuker A,MesséSR.
Timing of Initiation of Oral Anticoagulation after Acute Ischemic Stroke in Patients with Atrial Fibrillation.
Pharmacotherapy.
2020;40(1):55-71.
Periprocedural Intravenous Heparin During Endovascular Treatment for Ischemic Stroke: Results From the MR CLEAN Registry.
Stroke.
2019;50(8):2147-2155.
[6]Abdul-Rahim AH,Fulton RL,Frank B,et al.
Association of improved outcome in acute ischaemic stroke patients with atrial fibrillation who receive early antithrombotic therapy:analysis from VISTA.
Eur J Neurol.
2015;22(7):1048-1055.
[7]Paciaroni M,Agnelli G,Falocci N,et al.
Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin-K Oral Anticoagulants(RAF-NOACs)Study.
J Am Heart Assoc.
2017;6(12):e007034.
[8]Smythe MA,Parker D, Garwood CL, Cuker A, Messé SR.
Timing of Initiation of Oral Anticoagulation after Acute Ischemic Stroke in Patients with Atrial Fibrillation.
Pharmacotherapy.
2020;40(1):55-71.
Periprocedural Intravenous Heparin During Endovascular Treatment for Ischemic Stroke: Results From the MR CLEAN Registry.
Stroke.
2019;50(8):2147-2155.
[6]Abdul-Rahim AH,Fulton RL,Frank B,et al.
Association of improved outcome in acute ischaemic stroke patients with atrial fibrillation who receive early antithrombotic therapy:analysis from VISTA.
Eur J Neurol.
2015;22(7):1048-1055.
[7]Paciaroni M,Agnelli G,Falocci N,et al.
Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin-K Oral Anticoagulants(RAF-NOACs)Study.
J Am Heart Assoc.
2017;6(12):e007034.
[8]Smythe MA,Parker D, Garwood CL, Cuker A, Messé SR.
Timing of Initiation of Oral Anticoagulation after Acute Ischemic Stroke in Patients with Atrial Fibrillation.
Pharmacotherapy.
2020;40(1):55-71.
.
What is the role of anticoagulant therapy in the early treatment of AIS? At the 24th National Neurology Academic Conference of the Chinese Medical Association, Professor Zhang Meng from Daping Hospital of the Army Military Medical University sorted out the relevant content of AIS early anticoagulation in detail, including anticoagulation before, during and after thrombus removal.
He also shared his own clinical practice experience
.
Anticoagulation before thrombus removal.
Review the development process of anticoagulation drugs (Figure 1).
From the earliest unfractioned heparin (UFH) to the direct factor Xa antagonist for more than ten years, anticoagulation drugs have moved from multiple targets to Single-target therapy transitions while ensuring its activity and safety
.
Figure 1: The development process of anticoagulant drugs (picture from Professor Zhang Meng's PPT) ■ The previous research PROACT study, namely Prolyse in Acute Cerebral Thromboembolism, is a milestone study of arterial thrombolysis.
Both studies used the anticoagulant drug UFH
.
The results of the PROACT Ⅰ study showed that 81.
8% of patients in the high-dose UFH (100 IU/kg bolus+1000 IU/h×4 h) group achieved vascular recanalization (TIM1 blood flow classification 2 and 3), and the incidence of intracranial hemorrhage was 27.
3 %; In the low-dose group (2000 IU Bolus+500 IU/h×4 h), the incidence of intracranial hemorrhage dropped to 6.
7%, but the recanalization rate also dropped to 40% [1]
.
The results of the PROACTⅡ study showed that intraarterial administration of recombinant prourokinase (rPro-UK) combined with UFH within 6 hours of acute cerebral infarction compared with low-dose UFH, although increased the incidence of intracranial hemorrhage, can significantly improve the 90-day good prognosis [ 2]
.
In 2015, a systematic review reviewed 24 RCT studies on early anticoagulation treatment of AlS from 2008 to 2014, (21 of which used UFH), 23748 patients, and the results showed that anticoagulation therapy can reduce the recurrence rate of AlS , Pulmonary embolism and deep vein thrombosis rates, but are offset by the increased risk of intracranial hemorrhage [3]
.
Current guidelines, such as the 2019 AHA/ASA Guidelines for Early Management of Acute Ischemic Stroke, do not recommend emergency anticoagulation for patients with acute ischemic stroke to prevent early stroke recurrence, deterioration of tissue and nerve function, or improve prognosis
.
■ Anticoagulation promotes the recovery of AIS patients-case sharing Although the guidelines do not recommend preoperative anticoagulation, in actual clinical practice, preoperative anticoagulation may be used to promote the recovery of patients
.
Professor Zhang shared similar cases .
The 52-year-old patient was admitted to the hospital for "dizziness, blurred vision for 5 days, and weakness of the right limb for 4 days"
.
The National Institutes of Health Stroke Scale (NIHSS) score was 13 points, and the ASPECT score was 3 points
.
The imaging examination is shown in Figure 2, and the internal carotid artery dissection is suspected
.
During the treatment, patients were given 3000u heparin before surgery, 0.
4ml Bid of low molecular weight heparin (LMWH) after surgery, and then transitioned to warfarin
.
The patient's treatment check result is shown in Figure 3
.
After 11 months of treatment, the patient's internal carotid artery repair effect was better (Figure 4)
.
This case shows that anticoagulation therapy has a significant effect on specific acute large vessel occlusion (LVO) AIS
.
Figure 2: Admission imaging examination (picture from Professor Zhang Meng's PPT) Figure 3: Patient treatment examination results (picture from Professor Zhang Meng's PPT) Figure 4: Comparison after 11 months of treatment (picture from Professor Zhang Meng's PPT) Embolectomy In 2018, Winningham et al.
retrospectively analyzed the TREVO2 trial.
53 patients (53/173) received an average of 3000 U intravenous UFH during the perioperative period.
The results showed that the 90-day good prognosis of patients was related to intravenous UFH, and intracranial hemorrhage occurred.
The rate difference is not statistically significant [4]
.
In the MR CLEAN study (ie, Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke Study), 1488 patients were analyzed in the same case.
Among them, 398 patients (27%) received intravenous UFH treatment (median dose 5000 U), two There was no significant difference in functional prognosis (Figure 5), successful recanalization rate, incidence of intracranial hemorrhage, and mortality between the groups.
However, the prognosis of patients is better in treatment centers with a higher proportion of UFH [5]
.
In these studies, the incidence of intracranial hemorrhage was between 5%-12%
.
Overall, the risk of intracranial hemorrhage seems to be offset by a higher overall good functional prognosis, suggesting that UFH may be beneficial to administering UFH during arterial therapy
.
Figure 5: Comparison of mRs scores between the two groups with and without heparin in the MR CLEAN study [5] Professor Zhang introduced the intraoperative heparin administration program in his center: For patients who did not receive intravenous thrombolysis before surgery, surgery started After that, UFH 3000U is usually given as an intravenous bolus, and 500U is added every hour thereafter
.
For patients who receive intravenous thrombolysis within 2 hours before surgery, UFH is generally not given.
For patients with an interval of more than 2 hours, depending on whether there is a tendency for hypercoagulability during surgery, an appropriate amount of UFH should be given
.
It is more reasonable to monitor the activated coagulation time (ACT) during the operation and adjust the dosage based on this
.
Anticoagulation after thrombus removal Although this part of the report is an anticoagulation strategy after thrombus removal, Professor Zhang mainly introduces anticoagulation treatment after stroke in patients with atrial fibrillation
.
■ The VISTA study on the timing of anticoagulation after the occurrence of AIS in atrial fibrillation (the Virtual International Stroke Trials Archive study) showed that vitamin K antagonist treatment started 2-3 days after the onset of stroke in patients with atrial fibrillation, compared with the start of use> 3 days, ischemic The probability of stroke recurrence is lower, and the 90-day functional recovery of the anticoagulation group is better [6]
.
The RAF-NOAC study (ie Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin-K Oral Anticoagulants study) shows that: most intracranial hemorrhage occurs in patients who initiate anticoagulation <3 days after stroke : The probability of stroke recurrence or bleeding in patients who started new oral anticoagulants within 2 days was 12.
4%, 2.
1% after 3-14 days, and 9.
1% after 14 days
.
However, these bleeding occurred 30 days after medication, and the relationship with early anticoagulation is not clear
.
In 2020, a systematic review analyzed the relevant literature on early anti-doubt treatment after stroke since 1990.
The systematic review pointed out [8]: The use of parenteral anticoagulants within 48 hours leads to an increased risk of hemorrhagic transformation and is not recommended; within 48 hours The use of new oral anticoagulants is associated with 5% of hemorrhage conversion.
There is not enough data to support the safety of starting conventional oral anticoagulants (new oral anticoagulants or warfarin) within 48 hours after AIS
.
■ Guidelines for the recommendation of anticoagulation after AIS in patients with atrial fibrillation.
The 2019 American Heart Association/American Stroke Association (AHA/ASA) early management guidelines for acute ischemic stroke are recommended for most patients with acute ischemic stroke with atrial fibrillation It is reasonable to start oral anticoagulation therapy between 4 and 14 days after the onset of neurological symptoms
.
The Chinese Guidelines for Endovascular Treatment of Acute Ischemic Stroke in China 2018 recommend that anticoagulation treatment after intravenous thrombolysis and intravascular treatment is still inconclusive.
Early anticoagulation treatment without choice is not recommended.
A few special patients are in You can choose carefully after carefully evaluating the risk-benefit ratio
.
For acute ischemic stroke caused by atrial fibrillation, it is reasonable to start anticoagulant therapy 4-14 days after the onset
.
In 2016, the European Heart Association recommended the 1-3-6-12 rule for the timing of starting or continuing anticoagulation therapy after a stroke or transient ischemic attack.
In simple terms, it means that the timing of the restart of a transient ischemic attack is after the occurrence1 Day, mild stroke (NIHSS <8 points) 3 days, moderate stroke (NIHSS score 8-15 points) 6 days, severe stroke (NIHSS ≥ 16 points) 12 days
.
See Figure 6 for details
.
Figure 6: Timing of starting or continuing anticoagulation after stroke or transient cerebral ischemia (picture adapted from Professor Zhang Meng's PPT) Professor Zhang concluded that the purpose of early anticoagulation after thrombus removal is to prevent reocclusion and improve microcirculation , That is, to block the vicious circle of blocked venous return and intracranial hypertension
.
Early anticoagulation treatment of AIS, to clarify the type of anticoagulation patient, the timing of anticoagulation, the type and dosage of anticoagulation drugs, we still need to continue to explore
.
The content of this article is compiled from the lecture of Professor Zhang Meng at the 24th National Neurology Conference of the Chinese Medical Association-"Thinking of Early Anticoagulation after AIS"
.
References: [1]del Zoppo GJ,Higashida RT,Furlan AJ,Pessin MS,Rowley HA,Gent M.
PROACT:a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke.
PROACT Investigators .
Prolyse in Acute Cerebral Thromboembolism.
Stroke.
1998;29(1):4-11.
[2]Furlan A,Higashida R,Wechsler L,et al.
Intra-arterial prourokinase for acute ischemic stroke.
The PROACT II study:a randomized controlled trial.
Prolyse in Acute Cerebral Thromboembolism.
JAMA.
1999;282(21):2003-2011.
[3]Sandercock PA,Counsell C,Kane EJ.
Anticoagulants for acute ischaemic stroke.
Cochrane Database Syst Rev.
2015;2015( 3):CD000024.
Published 2015 Mar 12.
[4]Winningham MJ,Haussen DC,Nogueira RG,et al.
Periprocedural heparin use in acute ischemic stroke endovascular therapy:the TREVO 2 trial.
J Neurointerv Surg.
2018;10(7) :611-614.
[5]van de Graaf RA,Chalos V,van Es ACGM,et al.
Periprocedural Intravenous Heparin During Endovascular Treatment for Ischemic Stroke: Results From the MR CLEAN Registry.
Stroke.
2019;50(8):2147-2155.
[6]Abdul-Rahim AH,Fulton RL,Frank B ,et al.
Association of improved outcome in acute ischaemic stroke patients with atrial fibrillation who receive early antithrombotic therapy:analysis from VISTA.
Eur J Neurol.
2015;22(7):1048-1055.
[7]Paciaroni M,Agnelli G, Falocci N, et al.
Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin-K Oral Anticoagulants(RAF-NOACs) Study.
J Am Heart Assoc.
2017;6(12):e007034.
[8]Smythe MA,Parker D,Garwood CL,Cuker A,MesséSR.
Timing of Initiation of Oral Anticoagulation after Acute Ischemic Stroke in Patients with Atrial Fibrillation.
Pharmacotherapy.
2020;40(1):55-71.
Periprocedural Intravenous Heparin During Endovascular Treatment for Ischemic Stroke: Results From the MR CLEAN Registry.
Stroke.
2019;50(8):2147-2155.
[6]Abdul-Rahim AH,Fulton RL,Frank B,et al.
Association of improved outcome in acute ischaemic stroke patients with atrial fibrillation who receive early antithrombotic therapy:analysis from VISTA.
Eur J Neurol.
2015;22(7):1048-1055.
[7]Paciaroni M,Agnelli G,Falocci N,et al.
Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin-K Oral Anticoagulants(RAF-NOACs)Study.
J Am Heart Assoc.
2017;6(12):e007034.
[8]Smythe MA,Parker D, Garwood CL, Cuker A, Messé SR.
Timing of Initiation of Oral Anticoagulation after Acute Ischemic Stroke in Patients with Atrial Fibrillation.
Pharmacotherapy.
2020;40(1):55-71.
Periprocedural Intravenous Heparin During Endovascular Treatment for Ischemic Stroke: Results From the MR CLEAN Registry.
Stroke.
2019;50(8):2147-2155.
[6]Abdul-Rahim AH,Fulton RL,Frank B,et al.
Association of improved outcome in acute ischaemic stroke patients with atrial fibrillation who receive early antithrombotic therapy:analysis from VISTA.
Eur J Neurol.
2015;22(7):1048-1055.
[7]Paciaroni M,Agnelli G,Falocci N,et al.
Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin-K Oral Anticoagulants(RAF-NOACs)Study.
J Am Heart Assoc.
2017;6(12):e007034.
[8]Smythe MA,Parker D, Garwood CL, Cuker A, Messé SR.
Timing of Initiation of Oral Anticoagulation after Acute Ischemic Stroke in Patients with Atrial Fibrillation.
Pharmacotherapy.
2020;40(1):55-71.
